Article ; Online: The bottom-up approach to bounding potential low-dose cancer risks from formaldehyde: An update.
Regulatory toxicology and pharmacology : RTP
2016 Volume 77, Page(s) 167–174
Abstract: In 2013, we proposed a novel bottom-up approach to bounding low-dose cancer risks that may result from small exogenous exposures to chemicals that are always present in the body as a result of normal biological processes. The approach utilizes the ... ...
| Abstract | In 2013, we proposed a novel bottom-up approach to bounding low-dose cancer risks that may result from small exogenous exposures to chemicals that are always present in the body as a result of normal biological processes. The approach utilizes the background cancer risk and the background (endogenous) concentration of a cancer-related exposure biomarker in specific target tissues. After allowing for statistical uncertainty in these two parameters, the ratio of the background risk to background exposure provides a conservative slope factor estimate that can be utilized to bound the added risk that may be associated with incremental exogenous exposures. Our original bottom-up estimates were markedly smaller than those obtained previously by the US Environmental Protection Agency (USEPA) with a conventional top-down approach to modeling nasopharyngeal cancer and leukemia mortality data from a US worker cohort. Herein we provide updated bottom-up estimates of risk for these two cancers that are smaller still, and rely upon more robust estimates of endogenous and exogenous formaldehyde-DNA adducts in monkeys and a more robust estimate of the DNA adduct elimination half-life in rats, both obtained very recently. We also re-examine the worker mortality data used by USEPA in developing its estimate of human leukemia incidence from lifetime exposure to 1 ppm airborne formaldehyde. Finally, we compare a new bottom-up slope estimate of the risk of rat nasal cancer with conventional top-down estimates obtained with empirical dose-response modeling of rat nasal cancer bioassay data. |
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| MeSH term(s) | Animals ; Carcinogenicity Tests/methods ; Carcinoma ; DNA Adducts/genetics ; DNA Adducts/metabolism ; Dose-Response Relationship, Drug ; Fixatives/pharmacokinetics ; Fixatives/toxicity ; Formaldehyde/pharmacokinetics ; Formaldehyde/toxicity ; Haplorhini ; Humans ; Inhalation Exposure/adverse effects ; Leukemia/chemically induced ; Leukemia/genetics ; Leukemia/metabolism ; Leukemia/mortality ; Models, Statistical ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/chemically induced ; Nasopharyngeal Neoplasms/genetics ; Nasopharyngeal Neoplasms/metabolism ; Nasopharyngeal Neoplasms/mortality ; Rats ; Risk Assessment ; Species Specificity ; Uncertainty |
| Chemical Substances | DNA Adducts ; Fixatives ; Formaldehyde (1HG84L3525) |
| Language | English |
| Publishing date | 2016-02-04 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 604672-1 |
| ISSN | 1096-0295 ; 0273-2300 |
| ISSN (online) | 1096-0295 |
| ISSN | 0273-2300 |
| DOI | 10.1016/j.yrtph.2016.01.021 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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